RhoB regulation pathway
Ras homolog gene family, member A (RhoB) is a member of a
family of small GTPases. Rho GTPases control multiple cellular processes, including actin
and microtubule dynamics, gene expression, the cell cycle, cell polarity and membrane
transport through their ability to bind to numerous downstream effectors that lead to
diverse parallel downstream signaling pathways 7749321, .
There are several classes of regulatory proteins that affect the activation state of
RhoB. Guanine nucleotide exchange factors (GEFs) promote
exchange of GTP for GDP, thereby activate Rho proteins. Rho/rac guanine nucleotide
exchange factor (GEF) 2 (ARHGEF2) and Rho guanine nucleotide
exchange factor (GEF) 3 (ARHGEF3) are known GEFs for
RhoB , . Vav 2 guanine
nucleotide exchange factor (VAV-2) and Rho guanine
nucleotide exchange factor (GEF) 10-like (GrinchGEF) also
can stimulate activity of RhoB , .
Geranylgeranyltransferase type I (GGTase-I) and
Farnesyltransferase CAAX box (FTase) promote
post-translational modification of RhoB protein by
geranylgeranylation and farnesylation. It is also essential for
RhoB biological activity , .
Guaninenucleotide-dissociation inhibitors (GDIs) bind to prenylated GDP-bound Rho
proteins and allow translocation between membranes and the cytosol . The
most known RhoB GDIs are Rho GDP dissociation inhibitors
(GDI) alpha and gamma (RhoGDI alpha and RhoGDI
gamma). They bind to RhoB and suppress its
activation , .
Once activated, the GTPases bind to a spectrum of effectors to stimulate downstream
signaling pathways. RhoB binding to key effectors Diaphanous
homolog 1, 3 (DIA1, mDIA2(DIAPH3)) and Rhophilin Rho GTPase
binding protein 2 (Rhophilin 2) leads to actin
polymerization and cytoskeleton rearrangements and also regulates endosomal trafficking
, , . Protein kinase N1
(PRK1) and Rhotekin are also
well-known RhoB downstream effectors , . And finally, RhoB can directly bind to
Phospholipase C epsilon 1 (PLC-epsilon 1) and stimulate its
enzymatic activity , .
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